tbuckley/cabot-search huggingface dataset:
RETooling the RET Inhibitor Pralsetinib for ESR1 Fusion–Positive Breast Cancer and Beyond
Authors: Jie Wu, Vivek Subbiah
Journal: Cancer Research (2023)

Transcriptionally active fusions of ESR1 (ESR1-TAF) and somatic mutations in the estrogen receptor alpha (ERα) ligand-binding domain (LBD) cause endocrine therapy resistance in breast cancer. In searching for therapeutic target kinase(s) in these breast cancers, Gou and colleagues identified FLT4, RET, JAK1, and IGF1R as the top upregulated kinases induced by ESR1-TAFs and ERα LBD mutants in breast cancer cells. Among them, inhibition of RET by pralsetinib suppressed ESR1-TAF-driven and ERα LBD mutant-driven cell proliferation and patient-derived xenograft growth. Pralsetinib is an inhibitor of the RET protein tyrosine kinase that is approved for treating oncogenic RET mutation-positive and RET fusion-positive thyroid cancers and non-small cell lung cancer. The work by Gou and colleagues reinforces the knowledge of RET as an ESR1 target gene and highlights that RET interacts with ERα to promote breast cancer tumorigenesis and antiestrogen resistance. It also raises the prospect of repositioning pralsetinib to target wildtype RET in ER-positive breast cancer. See related article by Gou et al., p. 3237.
Emoji use validates the potential for meaning standardization among ideographic symbols
Authors: Laurie Beth Feldman
Journal: Behavioral and Brain Sciences (2023)

Abstract Technological innovations for online communication reduce the impact of signal transience on meaning standardization while boosting access to reliable patterning across multiple linguistic and nonlinguistic contexts – both asynchronous and synchronous. We classify emojis as ideographic symbols, examine their interdependence with surrounding words when reading/writing, and argue that emoji use validates the potential for meaning standardization in ideographs.
Diabetes and Immune Checkpoint Inhibitors—Letter
Authors: Sai Yendamuri, Santosh Patnaik
Journal: Clinical Cancer Research (2023)

Cortellini and colleagues have reported a detrimental effect of metformin on outcomes of immune checkpoint inhibition (ICI) therapy for advanced solid tumors (54% non–small cell lung cancer, NSCLC) in patients with type 2 diabetes mellitus (DM; ref. 1). The same group of investigators has previously noted that overweight and obese patients—body mass index (BMI) ≥ 25—with advanced solid tumors (65% NSCLC; type 2 DM status not reported) responded better to programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) ICI than those with a smaller BMI (2), in agreement with conclusions of other similar studies. We therefore request the authors to report in their new study the influence of BMI on the association of metformin use and ICI outcome. There are enough observations today to warrant stratified analyses of outcomes of ICI and other targeted therapies by overweight and obesity, including ours suggesting that metformin use reduces expression of immune checkpoint genes, including those encoding PD-1 and PDL-1, in NSCLC tumors of only the overweight or obese but not others (3). Indeed, a lack of consideration of obesity in the outcome analysis may explain why the harmful effect of metformin on ICI that is reported in this study is at discordance with studies reporting either a beneficial effect (4) or no effect (5) of metformin on response of patients with type 2 DM to ICI therapy for advanced NSCLC.See the Response, p. 4017S. Yendamuri reports grants from Lumeda Inc outside the submitted work. No disclosures were reported by the other author.
Underlying Causes of TIA and Minor Ischemic Stroke and Risk of Major Vascular Events
Authors: Philippa C. Lavallée, Hugo Charles, Gregory W. Albers, Louis R. Caplan, Geoffrey A. Donnan, José M. Ferro, Michael G. Hennerici, Julien Labreuche, Carlos Molina, Peter M. Rothwell, Philippe Gabriel Steg, Pierre-Jean Touboul, Shinichiro Uchiyama, Éric Vicaut, Lawrence K. S. Wong, Pierre Amarenco, Sebastian Ameriso, Claudia Nora Gandolfo, Guillermo Povedano, Javier Sagesse, Heman Pavon, Jorge Cancino, Walter Toledo, Yinin Huang, Xiping Gong, Yeato Martin, Donghu Mi, Tian Song, Yilong Wang, Yongjun Wang, Fran Chandgfend, Guo Contago, Jiao Hongyun, Heman Intao, Wu Jixing, Song Liquing, Tai Liwen, Liu Ran, Tian Shujuan, Liu Wenhong, Tak Hong Soi, Lawrence Wong, Liu Roxanna, Roman Flasar, Bedriska Ziktova, Michael Reif, Daniel Sanak Goldemund, Jiri Neumann, Dagmar Svakov, Daniel Sanak, Michael Kral, David Skoloudik, Daniel Vaclavik, Martin Kuhila, Pierre Amarenco, Lucie Cabrejo, Céline Guidoux, Cristina Maria Hobeanu, Philippa Lavallée, Elena Meseguer, Henrich Audebert, Daniel Menger, Wofgang Heide, Saskia Lipp, Huriye Ozalp, Christine Sctzmann, Christian Weimar, Katharina Platzbecker, Peter Ringleb, Michel G Hennerici, Martin Griebe, Katrin Knoll Olaf, Olaf Willmann, Juergen Harmut Faiss, Susan Dilan, Anja Kobersteein, Katarina Krimmer, Sandra Tietz, Peter Wienecke, Gerhard Hamann, Nico Burkhardt, Martin Liebetrau, Nadine Mueller, Michaela Wagner, Dr Strivastava, Peter Kelly, Hashomer David Tanne, Milena Cavazzuti, Sabrina Anticoli, Danilo Toni, Ken Nagata, Yasushi Okada, Hiroshi Yamagami, Kazuo Minematsu, Jojo Nakagawara, Shinchiro Uchiyama, Byung Chui Lee, Byung Woo Yoon, Ji Hoe, Jong Moo Park, Halim Abboud, Salam Koussa, Adnan Awada, Kay Sin Tan, Antonio Arauz, Frnando Gongora, Adrian Infante Valenzuela, Juan M. Esamilla, Patricia Canhao, ******- Ferro, Ana Catarina Fonseca, Manuel Correia, Assuncao Tuna, Nada Sternic, Milija Mijajlovic, Beata Dupejova, Jana Szedelyova, Renata Smirkova, Tomas Segura, Carlos Molina, Ana Rodriguez, Yolanda Silva, Javier Tejada, Francisco Purroy, Jaime Masjuan, Jose Vivancos, Ernest Palomeras, Miguel Angel Gamemro, JF Arenillas, Anna Calleja, Esther Rojo, Alastair Buchan, Peter Rothwell, Tsong Hai Lee, Ku Chou Chang, Yu-Ching Huang, Ruey-Tay Lin, Somsak Timkao
Journal: JAMA Neurology (2023)

The coexistence of underlying causes in patients with transient ischemic attack (TIA) or minor ischemic stroke as well as their associated 5-year risks are not well known.
Reevaluating the Association Between Autism and Lithium Exposure During Pregnancy
Authors: Rebecca Strawbridge, Allan H. Young
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Probiotics, Prebiotics, and Lactoferrin—Implications for Preterm Mortality and Morbidity
Authors: Mohan Pammi, Barbara B. Warner, Ravi Mangal Patel
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Harmonizing Definitions for Progression Independent of Relapse Activity in Multiple Sclerosis
Authors: Jannis Müller, Alessandro Cagol, Johannes Lorscheider, Charidimos Tsagkas, Pascal Benkert, Özgür Yaldizli, Jens Kuhle, Tobias Derfuss, Maria Pia Sormani, Alan Thompson, Cristina Granziera, Ludwig Kappos
Journal: JAMA Neurology (2023)

Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (RRMS). To date, there is no uniform agreed-upon definition of PIRA, limiting the comparability of published studies.
Ideography in interaction
Authors: Greta Gandolfi, Martin J Pickering
Journal: Behavioral and Brain Sciences (2023)

The standardization account predicts short message service (SMS) interactions, allowed by current technology, will support the use and conventionalization of ideographs. Relying on psycholinguistic theories of dialogue, we argue that ideographs (such as emoji) can be used by interlocutors in SMS interactions, so that the main contributor can use them to accompany language and the addressee can use them as stand-alone feedback.
Multisite Oral Amoxicillin Challenges During Pediatric Emergency Department Visits
Authors: David Vyles, George Hoganson, Constance McAneney, Mariana Castells, Elizabeth J. Phillips, Alexis Visotcky, David C. Brousseau
Journal: JAMA Pediatrics (2023)

This cohort study assesses differences in children’s allergy risk level designation and results of a direct oral challenge via a penicillin allergy delabeling process.
Porous silicon embedded in a thermoresponsive hydrogel for intranasal delivery of lipophilic drugs to treat rhinosinusitis
Authors: Shrishty Bakshi, Preeti Pandey, Yousuf Mohammed, Joanna Wang, Michael J. Sailor, Amirali Popat, Harendra S. Parekh, Tushar Kumeria
Journal: Journal of Controlled Release (2023)

Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an infection and inflammation of the nasal mucosa. However, localised delivery of lipophilic drugs for persistent nasal inflammation is a challenge especially with traditional topical nasal sprays. In this study, a composite thermoresponsive hydrogel is developed and tuned to obtain desired rheological and physiochemical properties suitable for intranasal administration of lipophilic drugs. The composite is comprised of drug-loaded porous silicon (pSi) particles embedded in a poloxamer 407 (P407) hydrogel matrix. Mometasone Furoate (MF), a lipophilic corticosteroid (log P of 4.11), is used as the drug, which is loaded onto pSi particles at a loading capacity of 28 wt%. The MF-loaded pSi particles (MF@pSi) are incorporated into the P407-based thermoresponsive hydrogel (HG) matrix to form the composite hydrogel (MF@pSi-HG) with a final drug content ranging between 0.1 wt% to 0.5 wt%. Rheomechanical studies indicate that the MF@pSi component exerts a minimal impact on gelation temperature or strength of the hydrogel host. The in-vitro release of the MF payload from MF@pSi-HG shows a pronounced increase in the amount of drug released over 8 h (4.5 to 21-fold) in comparison to controls consisting of pure MF incorporated in hydrogel (MF@HG), indicating an improvement in kinetic solubility of MF upon loading into pSi. Ex-vivo toxicity studies conducted on human nasal mucosal tissue show no adverse effect from exposure to either pure HG or the MF@pSi-HG formulation, even at the highest drug content of 0.5 wt%. Experiments on human nasal mucosal tissue show the MF@pSi-HG formulation deposits a quantity of MF into the tissues within 8 h that is >19 times greater than the MF@HG control (194 ± 7 μg of MF/g of tissue vs. <10 μg of MF/g of tissue, respectively).
How standardized must a code be to be useful?
Authors: Andrew M. Riggsby
Journal: Behavioral and Brain Sciences (2023)

Abstract If, as it appears, failure of standardization blocks the rise of general-purpose ideography, then a more precise characterization of “standardization” should help illuminate aspects of the process. Comparison is made with several histories of standardization to outline relevant dimensions and thresholds. This line of inquiry is particularly important for the forward-looking question of whether such ideography can ever arise.
Nirmatrelvir-Ritonavir and COVID-19 Mortality and Hospitalization Among Patients With Vulnerability to COVID-19 Complications
Authors: Colin R. Dormuth, Jason D. Kim, Anat Fisher, Jolanta Piszczek, I Fan Kuo
Journal: JAMA Network Open (2023)

Importance Postmarket analysis of individuals who receive nirmatrelvir and ritonavir (Paxlovid [Pfizer]) is essential because they differ substantially from individuals included in published clinical trials. Objective To examine the association of nirmatrelvir and ritonavir with prevention of death or admission to hospital in individuals with different risks of complications from COVID-19 infection. Design, Setting, and Participants This is a cohort study of adult patients in British Columbia, Canada, between February 1, 2022, and February 3, 2023. Patients were eligible if they belonged to 1 of 4 higher-risk groups of individuals who received priority for COVID-19 vaccination. Two groups included clinically extremely vulnerable (CEV) people who were severely (CEV1) or moderately immunocompromised (CEV2). CEV3 individuals were not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group was added to allow wider access to nirmatrelvir and ritonavir for certain other higher-risk individuals who were not in a CEV group, such as those older than 70 years who were unvaccinated. Exposures Patients with COVID-19 who received nirmatrelvir and ritonavir were matched to patients in the same vulnerability group; who were of the same sex, age, and propensity score for nirmatrelvir and ritonavir treatment; and who were also infected within 1 month of the individual treated with nirmatrelvir and ritonavir. Main Outcomes and Measures The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days. Results There were 6866 individuals included in the study, of whom 3888 (56.6%) were female and whose median (IQR) age was 70 (57-80) years. Compared with unexposed controls, treatment with nirmatrelvir and ritonavir was associated with statistically significant relative reductions in the primary outcome in the CEV1 group (560 patients; risk difference [RD], −2.5%, 95% CI, −4.8% to −0.2%) and the CEV2 group (2628 patients; RD, −1.7%; 95% CI, −2.9% to −0.5%). In the CEV3 group, the RD was −1.3%, but the findings were not statistically significant (2100 patients; 95% CI, −2.8% to 0.1%). In the EXEL group, treatment was associated with higher risk of the outcome (RD, 1.0%), but the findings were not statistically significant (1578 patients; 95% CI, −0.9% to 2.9%). Conclusions and Relevance In this cohort study of 6866 individuals in British Columbia, nirmatrelvir and ritonavir treatment was associated with reduced risk of COVID-19 hospitalization or death in CEV individuals, with the greatest benefit observed in severely immunocompromised individuals. No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.
Notational systems are distinct cognitive systems with different material prehistories
Authors: Karenleigh A Overmann
Journal: Behavioral and Brain Sciences (2023)

Abstract Notations are cognitive systems involving distinctive psychological functions, behaviors, and material forms. Seen through this lens, two main types – semasiography and visible language – are fundamentally differentiated by their material prehistories, emphasis on iconography, and the centrality of language's combinatorial faculty. These fundamental differences suggest that key qualities (iconicity, expressiveness, concision) are difficult to conjoin in a single system.
Communication consistency, completeness, and complexity of digital ideography in trustworthy mobile extended reality
Authors: Kevin B. Clark
Journal: Behavioral and Brain Sciences (2023)

Abstract Communication barriers long-associated with ideographs, including combinatorial grapholinguistic complexity, computational encoding–decoding complexity, and technological rendering and deployment, become trivialized through advancements in interoperable smart mobile digital devices. Such technologies impart unprecedented extended-reality user hazards only mitigated by unprecedented colloquial and bureaucratic societal norms. Digital age norms thus influence natural ideographic language origins and evolution in ways novel to human history.
The different paths to cultural convergence
Authors: Larissa Mendoza Straffon, Aliki Papa, Heidi Øhrn, Andrea Bender
Journal: Behavioral and Brain Sciences (2023)

Abstract Morin envisions the adaptive landscape of graphic codes as an unfertile valley where writing rises as an isolated peak that humans managed to reach only on four occasions throughout all of history. By exploring the different paths to cultural convergence, we suggest an alternative landscape occupied by a mountain range of visual art systems. We conclude that graphic communication through visual art worked well enough to render writing contingent but not necessary in most cases.
Distinct Mechanisms of Resistance to CDK4/6 Inhibitors Require Specific Subsequent Treatment Strategies: One Size Does Not Fit All
Authors: Hannah F. Wingate, Khandan Keyomarsi
Journal: Cancer Research (2023)

Abstract Cyclin-dependent kinase (CDK) 4/6 inhibitors have transformed the treatment landscape of patients with hormone receptor–positive breast cancers. However, despite improvements in clinical outcomes, the approximately 70% of patients with tumors that are not intrinsically resistant to a CDK4/6 inhibitor still ultimately acquire resistance, which leads to a dilemma for clinicians when deciding which treatment to offer patients when they demonstrate disease progression on a CDK4/6 inhibitor. As such, many groups have sought to understand the mechanisms of resistance to CDK4/6 inhibitors, mostly focusing on genetic alterations associated with resistance. Though several recurrent mutations have been described, they are not consistent enough to guide clinical practice or generate novel rational treatment options. Two recent publications have used transcriptomic analysis to unravel distinct mechanisms driving resistance to individual CDK4/6 inhibitors and in doing so have identified biomarkers that could potentially help identify the next course of treatment for patients following disease progression.
Circulating Tumor DNA Analysis in Advanced Urothelial Carcinoma: Insights from Biological Analysis and Extended Clinical Follow-up
Authors: Sia V. Lindskrog, Karin Birkenkamp-Demtröder, Iver Nordentoft, George Laliotis, Philippe Lamy, Emil Christensen, Derrick Renner, Tine G. Andreasen, Naja Lange, Shruti Sharma, Adam C. ElNaggar, Minetta C. Liu, Himanshu Sethi, Alexey Aleshin, Mads Agerbæk, Jørgen B. Jensen, Lars Dyrskjøt
Journal: Clinical Cancer Research (2023)

Abstract Purpose: To investigate whether circulating tumor DNA (ctDNA) assessment in patients with muscle-invasive bladder cancer predicts treatment response and provides early detection of metastatic disease. Experimental Design: We present full follow-up results (median follow-up: 68 months) from a previously described cohort of 68 neoadjuvant chemotherapy (NAC)-treated patients who underwent longitudinal ctDNA testing (712 plasma samples). In addition, we performed ctDNA evaluation of 153 plasma samples collected before and after radical cystectomy (RC) in a separate cohort of 102 NAC-naïve patients (median follow-up: 72 months). Total RNA sequencing of tumors was performed to investigate biological characteristics of ctDNA shedding tumors. Results: Assessment of ctDNA after RC identified metastatic relapse with a sensitivity of 94% and specificity of 98% using the expanded follow-up data for the NAC-treated patients. ctDNA dynamics during NAC was independently associated with patient outcomes when adjusted for pathologic downstaging (HR = 4.7; P = 0.029). For the NAC-naïve patients, ctDNA was a prognostic predictor before (HR = 3.4; P = 0.0005) and after RC (HR = 17.8; P = 0.0002). No statistically significant difference in recurrence-free survival for patients without detectable ctDNA at diagnosis was observed between the cohorts. Baseline ctDNA positivity was associated with the Basal/Squamous (Ba/Sq) subtype and enrichment of epithelial-to-mesenchymal transition and cell cycle–associated gene sets. Conclusions: ctDNA is prognostic in NAC-treated and NAC-naïve patients with more than 5 years follow-up and outperforms pathologic downstaging in predicting treatment efficacy. Patients without detectable ctDNA at diagnosis may benefit significantly less from NAC, but additional studies are needed.
Fractals and artificial intelligence to decrypt ideography and understand the evolution of language
Authors: Cédric Sueur, Marie Pelé
Journal: Behavioral and Brain Sciences (2023)

Abstract Self-sufficient ideographies are rare because they are stifled by the issue of standardization. Similar issues arise with abstract art or drawings created by young children or great apes. We propose that mathematical indices and artificial intelligence can help us decode ideography, and if not to understand its meaning, at least to know that meaning exists.
Why the use of ideographic codes does not improve communicative skills in patients with severe aphasia?
Authors: Guido Gainotti
Journal: Behavioral and Brain Sciences (2023)

Abstract In his target article, Morin claims that ideographic codes are exceedingly difficult to use. In my commentary I will show that the use of Bliss symbols does not improve the communicative abilities of aphasic patients with severe language disorders. This failure to remediate communication disorders may result from disruption of inner language allowing to translate ideographic codes into spoken language.
A bigger problem for ideography: The pervasiveness of linguistic structure
Authors: Daniel Harbour
Journal: Behavioral and Brain Sciences (2023)

Abstract Writing systems display ubiquitous linguistic structure, from the recursive syntactic properties of their glyphs to the morphology/phonology of their combinatorics. This extends to Ancient Egyptian, Chinese, and Sumerian ideograms. Pure ideography requires switching this influence off. The pervasive linguistic tinge to the fabric of writing systems suggests that the chances of breaking what Morin terms language's lock-in effect are slim.
Mind the gap: Why is there no general purpose ideographic system?
Authors: Kim Sterelny
Journal: Behavioral and Brain Sciences (2023)

Morin has identified an intriguing puzzle about human communication systems, and one element of the solution: Inscriptional sign systems pose more coordination problems, making sender/receiver coadaptation more difficult. But I reject his view of written language, concluding that inscriptional sign systems can be generalist. The upshot is a cost-based proposal about why generalist ideographic systems are essentially unknown.